Award winner recognized for forward thinking

"When H5N1 hit the fan, my group was one of a few in the world that had managed a real outbreak of avian influenza. We knew a lot about outbreak management and about the virus itself. We were involved in an international task force that was in place to try and manage the epidemic."

Fortunately for the virologist, her distaste for dogma and predilection for thinking outside the box have served her well in her 20-year career.

Dr. Capua is director of the Department of Comparative Biomedical Sciences at the Istituto Zooprofilattico Sperimentale delle Venezie in Legnaro, Italy. It hosts one of the Food and Agriculture Organization and World Organisation for Animal Health (OIE) reference laboratories for avian influenza and Newcastle disease and the OIE Collaborating Centre for Diseases at the Human-Animal Interface.

Her staff of more than 70 provides diagnostic expertise globally and conducts cutting-edge research on influenza viruses and viral zoonoses. About a decade ago, her Italian laboratory helped turn the tide in the fight against the spread of H5N1 avian influenza, and she served as the catalyst for greater information sharing among laboratories, particularly between the animal health and public health disciplines.

For her efforts in these areas, Dr. Capua was honored with the 2011 Penn Vet World Leadership Award. The unrestricted award of $100,000 is given annually to a veterinarian who has dramatically changed the practice and image of the profession and substantially influenced the lives and careers of others.

Veterinary student Jonathan Lustgarten also received $100,000 through the annual Penn Vet Inspiration Award competition (see page 909). Both awards are underwritten by the Vernon and Shirley Hill Foundation.

Baptism by fire

Dr. Capua graduated from the University of Perugia Faculty of Veterinary Medicine in 1989.

By 1998, she had become head of the virology office at Istituto Zooprofilattico Sperimentale delle Venezie in Venice. Only two years later, a major outbreak of a highly pathogenic H7N1 influenza strain struck poultry farms stretching roughly from Milan to Venice, and her laboratory had been appointed as the nation's reference laboratory for the bird flu. Problem was, she hadn't worked with the virus before.

"This was the biggest outbreak there had ever been at the time. We had nobody to ask and nobody to give us advice except some scientists who had worked with smaller outbreaks or ones 20 years before. The scale and complexity of the industry had changed dramatically," Dr. Capua said.

Although the Italian government managed to quash the outbreak by culling more than 13 million poultry, a so-called low-pathogenic version of H7N1 kept circulating, and researchers feared it might revert without warning to the highly pathogenic version and kick off a new disaster.

That's when Dr. Capua and her team devised the DIVA (Differentiating Infected from Vaccinated Animals) strategy. Instead of basing a vaccine on the H7N1 strain already infecting poultry, they suggested using a closely related strain, H7N3. Vaccinated animals could be distinguished from infected ones because they would carry antibodies against the N3 variety instead of N1, the team argued.

And four months after the vaccination campaign went live in November 2000, the low-pathogenic strain of H7N1 was eliminated. A year later, when an H7N3 outbreak swept the area, the same trick was put in reverse, using an H7N1 vaccine.

Until that time, vaccination for avian influenza was verboten, especially for countries that have an export market. DIVA showed the international community that vaccination can be successful in controlling and eradicating avian influenza infection, provided it is used in combination with other measures, according to a Nov. 10, 2006, article in Science magazine.

Coincidentally, around this time the spread of the Asian H5N1 virus was starting to incite global fears.

"When H5N1 hit the fan, my group was one of a few in the world that had managed a real outbreak of avian influenza. We knew a lot about outbreak management and about the virus itself. We were involved in an international task force that was in place to try and manage the epidemic," Dr. Capua said.

More information sharing

By the mid-2000s, Dr. Capua's laboratory was receiving a steady stream of samples from H5N1-affected countries, primarily in the Middle East and Africa.

"When you receive a virus, in order to make any statement or conclusion on where it's from or how it will behave or what it looks like, you need to compare the sequence with isolates that had been obtained before," Dr. Capua said. "Whenever we obtained a new isolate, we asked other laboratories if we could compare it with their recent data, and they would refuse or require a material transfer agreement, which takes about six months to go through. I was getting irritated with this behavior. We were in a position where we had to draw conclusions from our work, but we couldn't because there were no points of reference available."

In February 2006, her laboratory characterized the Nigerian H5N1 strain. At the time, no one knew how the virus was spreading, making the first isolate from Africa important scientifically.

The World Health Organization asked her to deposit the sequence of a sample from Nigeria in a closed-off compartment of a flu database at Los Alamos National Laboratory in New Mexico, to which fewer than 20 laboratories have access. If she shared her sequence, WHO scientists said, she would have access to the rest of the restricted Los Alamos data.

"If we make information available only to a restricted number of laboratories, science and knowledge will progress in a slower way. Significant funding for research has been made available worldwide, and to be able to generate useful data, you need to select the correct viruses to work with, and you can only do this if surveillance data is readily available. ... International organizations had invested millions in labs and in training people in developing countries, but these scientists didn't have access to the big picture. It was a quite a contradiction," she said.

Dr. Capua chose to refuse the WHO's offer. Instead, she deposited H5N1 strains from Nigeria and Italy in GenBank for the entire world to see. At the same time, in a message on ProMED, an email list for emerging infectious diseases, she asked her colleagues to follow suit.

The incident sparked international debate and action on transparency issues on pathogens that impact public health.

OFFLU, the network of avian influenza expertise inaugurated jointly in 2005 by the FAO and OIE, immediately launched a campaign for openness. A month later, the network's Scientific Committee, which Dr. Capua chaired, decided to put new emphasis on the need for further collection, characterization, and exchange of avian flu viruses and for expansion of sequence data, the FAO reported.

The Global Initiative on Sharing All Influenza Data also was launched that year to share avian influenza sequences. GISAID continues to allow a better understanding of the evolving epidemiology of animal and human influenza infections by using a transdisciplinary approach, which is now a core part of the global influenza preparedness strategy.

Even the WHO, which initially defended the closed database, passed a resolution in 2011 defined as a landmark agreement "to ensure that in a pandemic, influenza virus samples will be shared with partners who need the information to take steps to protect public health."

"It's not something I achieved by myself. A lot of colleagues pushed for transparency and its importance, but I was the one who stood up and said we need to do something about this and change our approach," Dr. Capua said.

Looking back

One constant priority for Dr. Capua throughout her career, she says, has been questioning the status quo and not taking for granted what people have believed for many years.

More recently, she recalls when her laboratory reasoned that animal influenzas of the H1 and H3 subtype would be antigenically very different from the human viruses. Her staff performed some experimental work showing that cross-protection was much lower than expected. Dr. Capua warned the OIE, FAO, and WHO during a tripartite meeting in Paris that not only H5 but also H1 and H3 viruses could ignite a pandemic.

Her laboratory continues to work heavily with influenza and has since expanded its range to viruses from other species to try to understand host-pathogen interactions, their potential for causing various clinical conditions, and how viruses change. The staff works with major research institutes worldwide and has developed international collaborative projects that contribute substantially to the development of veterinary laboratory and diagnostic expertise in emerging countries.

Dr. Capua acknowledged that winning the leadership award is quite an accomplishment, particularly as the first female to do so and at the age of 45.

"I value a lot the significance of the award itself rather than the prize, which I'm thankful for, but I'd really like to make sure this international recognition is a seed we plant for a new way forward in veterinary public health and how veterinary medicine is perceived by international organizations and, ultimately, by the general public," she said.